The broad objective of this K01 mentored career development award is to obtain in depth research training and experience in the field of tumor immunology and dendritic cell (DC) biology, with the ultimate goal of becoming an independent investigator for developing novel anti-tumor treatment modalities. The research proposal is based on the hypothesis that DC subsets play a very important role in the initiation and regulation of anti-tumor immune response and their function will be affected by the tumor microenvironment and tumor-derived factors. For testing this hypothesis, we will study two specific aims, i.e., (1) Functional analysis and comparison of myeloid and lymphoid DC subsets; (2) Influence of the tumor derived factors on the antigen presentation function of different subsets of DC. The importance of this proposal lies in the fact that DC subsets are scarcely studied due to the difficulty of obtaining pure DC subsets and on the ground that highly pure DC subsets can be isolated from hFlex gene treated mice, which is a newly developed approach in this lab. The candidate is highly suited to perform the research. Dr. He is well trained in medicine, molecular biology, and gene delivery as documented in his 17 peer-reviewed publications and three submitted manuscripts. The candidate is committed to using the knowledge and techniques of gene delivery and molecular biology to study the DC biology and develop novel cancer treatment modalities. The two aims involve all the basic knowledge and techniques of modern immunology and biology. Incorporating the strong background in molecular biology the candidate already has with the training in tumor immunology and DC biology as he will receive through the proposed research., he will be positioned very well in the path towards an independent investigator in the field of developing new anti-tumor approaches by harnessing the knowledge and techniques of molecular biology, tumor immunology and DC biology. The environment the candidate chosen for this award is outstanding. The mentor, Dr. Louis D. Falo Jr., is well established and well funded in the field of tumor immunology and DC biology. The University of Pittsburgh Cancer Institute (UPCI) is well known for its strength in tumor immunology and DC application under the leadership of Drs. Ronald Herberman, Theresa Whiteside and Olivera Finn. The UPCI has the largest research team on DC biology and application. The departmental and institutional resources are excellent and the intellectual environment is superb as there are three well-established seminar series in the area of cancer biology, tumor immunology and DC biology and one journal club. In addition, other cancer related seminars are also available from other departments in the school of medicine. The institute is committed to fully support the candidate by providing access to all of the resources. Together, the candidate, research proposal, and the environment provide a strong application for this award.